Cytogenetic and molecular genetic analysis of small supernumerary marker chromosomes in fetal amniotic fluid

Objective: To explore the origin and mechanism of small supernumerary marker chromosomes (sSMC) in order to facilitate genetic counseling.

Methods: Chromosome karyotypes of two fetuses and their immediate family members were analyzed by conventional G banding. High-throughput whole genome sequencing was used to determine the origin of sSMCs.

Results: Fetus 1 was shown to have a karyotype of 47,XY,+mar but with normal FISH and B ultrasound findings. Its father also had a 47,XY,+mar karyotype with normal FISH results and clinical phenotype. High-throughput genome sequencing revealed that fetus 1 and its father were both 46,XY,dup(21)(q11.2;q21.1) with a 6.2 Mb duplication of the long arm of chromosome 21. The fetus was born with normal phenotype and developed well. Its grandmother also had a karyotype of 46,XX,t(15;21)(q13;p13) with normal FISH result and clinical phenotype. The karyotypes of its mother and grandfather were both normal. Analysis of fetus 2 showed a 47,XY,+mar karyotype with normal FISH results. High-throughput genome sequencing suggested a molecular karyotype of 46,XX. The fetus was born with normal phenotype and developed well. The karyotypes of its parents were both normal.

Conclusions: Considering their variable origins, identification of sSMC should combine conventional G banding analyses with high-throughput whole genome sequencing for precise delineation of the chromosomes.